Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• that of sulfinyl imines (S)-25c,d exhibiting an α-benzyloxy substituent provided high diastereoselectivities (76–88% de). This assumed the coordination of the α-alkoxy group to zinc. Even a higher diastereoselectivity of >90% de was achieved for more sterically hindered α-alkoxy-derived substrates (S

• (79–93% ee). Notably, even sterically hindered cyclic imines bearing two substituents were compatible, providing the corresponding products in high enantioselectivities (79–93% ee). Moreover, the use of ketimines in such reactions represented a challenge, owing to their low reactivity and steric

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• formed by addition from the less sterically hindered amino group. The free amino group was alkylated by reductive amination on reaction with substituted aldehyde or ketones to provide the corresponding pyrazolo[1,5-a]pyrimidine derivatives 139 (Scheme 39). The pyrazolo[1,5-a]pyrimidine derivatives 139

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• required for the conversion of electron-deficient derivatives. Besides, sterically hindered boronic acids were also tolerated in this reaction. This protocol was simplified and easy-to-handle and no protodeboronation byproduct was observed under these conditions, while the major side product (the

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• metalations of isoquinolines at C1 with sterically hindered amide bases like TMPMgCl∙LiCl (Knochel–Hauser base) [6]. For our present purpose, an appropriate 1-metalated isoquinoline species was to be converted into the corresponding 1-methyl product. Since the 7-hydroxy group of target alkaloid 1 is not

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• -iodoaniline 32 in 68% yield after isolation [52]. The cyclization was performed via nucleophilic aromatic substitution with DBU and DABCO. Presumably DABCO activates the chlorine and modifies it into a better leaving group allowing the sterically hindered base DBU to abstract a proton from the protected

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• group at position 2 is the most acidic, and the group at position 3 is most sterically hindered. Therefore, regioselective monosubstitution to positions 2 and 6 can be controlled by the amount and strength of the base used in the reaction, whereas monosubstitution at position 3 can be achieved by

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• system on glycosylation of 1α with several acceptors (Table 2). In all cases, reactions proceeded smoothly within 2–6 h and in good yields with moderate to good selectivity, as determined by the 1H and 13C NMR spectra. Glycosylation with less sterically hindered primary alcohols, e.g., allyl alcohol (2b

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• consecutive transformations. For instance, para-substituted halogenated anilines 3 (Table 5, entries 3–5) and ethyl 4-aminobenzoate (Table 5, entry 6) furnish the desired products in 51–65% yield. Interestingly, also sterically hindered anilines, such as 2,6-dimethylaniline can be obtained in 56% yield (Table

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• type 19 and cyclopropanes of type 15 in which Me2C is replaced by H2C was observed when the sterically hindered S-methanide derived from 2,2,6,6-tetramethylcyclohexanethione was reacted with E- or Z-1b [26], whereas in the cases of 2,2,5,5-tetramethylcyclopentanethione and 1,1,3,3-tetramethylindane-2

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• ). It is believed that the initially formed α-cyanooximes 85 undergo rapid cyclization to isoxazole derivatives 86. Interestingly, in the case of a more sterically hindered 3-chloronorcamphor oxime, the corresponding α-cyanooxime 85a was obtained, which did not undergo cyclization to isoxazole

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• acidification with hydrochloric acid. For example, the sterically hindered phenylphosphonic acid 85 was prepared in a two-step procedure starting from the dichlorophenylphosphine 83. Ph–PCl2 was first oxidized into the phenylphosphine oxide 84 with sulfuryl chloride in CCl4 and then hydrolysis occurred with

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• utilized glycosyl sulfoxide donors for glycosylation of unreactive substrates such as steroid derivative 2 by the Kahne group [25]. The axial C-7 hydroxy group in 2 is sterically hindered due to unfavorable 1,3-diaxial interactions. The traditional premixed glycosylation gave only low yields (<30%) of the

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• -type amine–isothiocyanate coupling reaction (Scheme 4). In the case of secondary amines (piperidine, morpholine and thiomorpholine) and sterically hindered amines (2,4- and 2,6-dimethylanilines), ball milling again resulted in ≥99% yields in 10 minutes, except for the reactions involving 4

• : corrugated chains of head-to-head or head-to-tail aligned molecules and discrete centrosymmetric dimers based on the R22(8) supramolecular synthon in the case of sterically hindered thioureas (Figure 2). The crystal structures of N,N'-diarylthioureas linked in chains via N–H···S hydrogen bonds can further be

• bis-thioureas which were tested as cyanide anion sensors in DMSO solution. Our group continued the research on the solid-state synthesis of thioureas focusing now on the reactivity of sterically hindered ortho-phenylenediamine (o-pda) with isothiocyanates [35]. Whereas Kaupp's approach to prepare a

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

• Wei Shi,
• Jingbo Yu,
• Zhijiang Jiang,
• Qiaoling Shao and
• Weike Su

Beilstein J. Org. Chem. 2017, 13, 1661–1668, doi:10.3762/bjoc.13.160

• sterically hindered substrate 1c led to a higher yield as compared with 1a and 1b, which is contrary to Li’s study [57] in solution-based Heck reactions. This might be because of the lone pairs of the oxygen atom in the keto group at the ortho-position could coordinate with Pd/MgAl-LDHs under HSBM conditions

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• propionamides 4a,b,h–k reacted readily under mild reaction conditions (Table 3, entries 1, 2, and 8–11), while for isobutyramide 4c a higher temperature was necessary (Table 3, entry 3). Finally, the more sterically hindered pivalamide 4d and the less reactive benzamides 4e–g required harsher reaction

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• formation of HPA dimer 11 and product of its decarboxylation 12 (Scheme 1). The formation of these two products (observed by 1H NMR) was recently reported by Knapp et al. [35] as a result from the treatment of HPA with a strong base (which was absent in our case). The failure to activate sterically hindered

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• of the eight DTMs which varied from 4.5 times greater than LMG for the most sterically hindered bromide derivative 2 to the least for the ortho-fluoride 4 with 0.6 less dose sensitivity than LMG (Table 1). This is also consistent for the ortho-methyl derivative 5 being more dose sensitive than it’s

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• stereoselective elimination and decarboxylation in situ. The corresponding aldehyde 22 was then homologated by an Abiko–Masamune anti-aldol addition [74] with ephedrine-derived ester 23, which proceeded with excellent yield and stereoselectivity. However, the subsequent removal of the sterically hindered chiral

Regioselective (thio)carbamoylation of 2,7-di-tert-butylpyrene at the 1-position with iso(thio)cyanates

• Anna Wrona-Piotrowicz,
• Marzena Witalewska,
• Janusz Zakrzewski and
• Anna Makal

Beilstein J. Org. Chem. 2017, 13, 1032–1038, doi:10.3762/bjoc.13.102

• , 6 and 8 of 1. However, Friedel–Crafts alkylation of 1 with an excess of sterically hindered tert-butyl chloride leads to 2,7-di-tert-butylpyrene (2) [8]. This compound, owing to the presence of two bulky and electron-donating tert-butyl groups, displays different reactivity towards electrophiles. It

• sterically hindered pyrene 1-position, whereas the bulkier protonated acetyl trifluoroacetate (the postulated electrophile in the examined Friedel–Crafts acylation) attacks sterically the less hindered 4-position. Conclusion We found that triflic acid-promoted (thio)carbamoylation of 2 with aliphatic iso

• sterically hindered pyrene framework. Experimental General All reagents were purchased from Sigma-Aldrich and used without further purification. Solvents were purified before use by reported methods. Column chromatography was carried out on silica gel 60 (0.040–0.063 mm, 230–400 mesh, Fluka). 1H and 13C NMR

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• homocoupling products 7a,b emerged as the predominant reaction products (Scheme 5, middle trace), probably due to preferable halogen–zinc exchange and subsequent homocoupling. Interestingly, such sterically hindered halides provided homocoupling products 7a,b in good yields (66% and 48%, respectively). The

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• several amine motifs. 4-Dimethylaminopyridine (DMAP) has been reported to assist in the sulfonylation and acylation of weak nucleophiles such as secondary amines, alcohols, amides, and sterically hindered amines when used as catalyst in addition to a base additive [28][29][30][31]. It has been suggested

• additive for sulfonylation of primary amines with o-NBS-Cl for the purpose of N-methylation on solid support. We herein report a DMAP-mediated strategy for the efficient regioselective N-methylation of sterically hindered primary amines as well as less hindered amines on solid support (Figure 1B). Our DFT

• electron-donating groups on the ring. Collidine has electron-donating groups that make it nucleophilic but it is sterically hindered, while DMAP is stabilized by resonance and much less hindered. Our results emphasized the effect of DMAP for the introduction of the o-NBS group as it proved the most

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• , and 1,4-dioxane/H2O as solvent (Scheme 1). Under these conditions, a wide range of aryl bromides and chlorides could be readily converted to the corresponding phenols in high yields at 100 °C within 1–18 h. Moreover, sterically hindered ortho-functionalized aryl halides and heteroaryl halides were

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• the first group was introduced in position 2, the substitution reaction at O-3 on the adjacent unit A was performed. Due to the lower reactivity of this alcohol group, an excess of base and electrophile was required for this step. In addition, the presence of the sterically hindered trityl-protected

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• state 5 containing two chromium ions bridged by a halogen. The less sterically hindered equatorial positions are occupied by the aldehyde substituent (R1 in Scheme 2) of 1 and halide group (X) of 3 and the aldehyde oxygen is thought to be coordinated to one of the Cr centres (the “coordinating” Cr

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• ) are applicable to this decyanation reaction. The use of hydrosilane as a mild reducing agent allows a high functional group tolerance (34b–e, 35, 39b, 43) and sterically hindered cyano groups are successfully removed (36, 41, 43). Reactions of benzyl cyanides proceed smoothly even in the absence of